Application of ginsenoside F5

Abstract

The invention provides application of ginsenoside F5. The ginsenoside F5 is used for reducing right ventricular systolic pressure, reducing right ventricular hypertrophy index, reversing vascular remodeling of pulmonary arterial hypertension and relieving pulmonary arterial vascular injury, and is used for preparing medicines for preventing and / or improving pulmonary arterial hypertension. The ginsenoside F5 can effectively improve pulmonary vascular remodeling of animals with pulmonary arterial hypertension, reduce right ventricular systolic pressure, relieve right ventricular hypertrophy, increase the survival rate of the animals with pulmonary arterial hypertension and relieve pulmonary artery vascular injury. The ginsenoside F5 has a certain improvement effect on the pulmonary arterial hypertension, is expected to become a new drug target for treating the pulmonary arterial hypertension, can be used as a drug for preventing and treating the pulmonary arterial hypertension, and is used for preventing and improving the pulmonary arterial hypertension.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medicine, and particularly relates to an application of ginsenoside F5. BACKGROUND

[0002] Pulmonary arterial hypertension (PAH) is a serious cardiovascular pathophysiological syndrome caused by various pathogenic factors, such as environmental factors, blood flow shear force changes, genetic and gene mutations, infections, and circulatory system changes. Primary or secondary to cardiopulmonary diseases or other diseases, in clinical practice, PAH can be diagnosed when the mean pulmonary arterial pressure is ≥25 mmHg, the pulmonary arteriolar wedge pressure is ≤15 mmHg, and the pulmonary vascular resistance is >3 Wood units, as measured by right heart catheterization at sea level in a resting state. The main pathological features are pulmonary vascular remodeling and right ventricular dysfunction. Persistent vasoconstriction, vascular stenosis or occlusion, and progressive increase in pulmonary vascular resistance lead to persistent elevation of pulmonary arterial pressure, and then secondary right ventricular hypertrophy and even right ventricular failure and even death. Although PAH has become a major disease in the global cardiovascular field that urgently needs to be broken through, the existing treatment strategies still have significant bottlenecks. The currently approved drugs in clinical practice mainly target the improvement of vasodilation function, including the prostacyclin pathway (epoprostenol, treprostinil, etc.), the endothelin-1 receptor axis (bosentan, ambrisentan), the nitric oxide-cGMP signal cascade (PDE-5 inhibitors, soluble guanylate cyclase agonists), and calcium channel blockers. Although the above-mentioned drugs can temporarily relieve the shortness of breath and chest pain symptoms of PAH patients after exercise and delay disease progression, they cannot block or reverse pulmonary vascular remodeling. Long-term follow-up shows that the incidence of end-stage right heart failure in patients remains high, and about 30% of individuals do not respond well to current combination therapy. Therefore, the development of multi-target drugs that can inhibit pulmonary vascular remodeling and improve vasodilation function not only can specifically reduce pulmonary vascular damage, but also is expected to reverse the PAH disease process from the source, becoming a key to the treatment and prevention of PAH.

[0003] According to the clinical symptoms of PAH, TCM classifies it into the categories of “asthma”, “pulmonary distension”, “phlegm retention”, “chest obstruction”, “pulmonary obstruction”, and “water and qi disease”, and often uses the treatment methods of warming yang, tonifying qi, promoting blood circulation, promoting water, and eliminating phlegm. The compound prescriptions / single herbs often play a therapeutic role in a synergistic mode, and have the advantages of multi-component, multi-target, and multi-pathway regulation. With the deepening understanding of the pathogenesis of PAH in TCM, traditional Chinese medicine has shown unique advantages in the intervention of pulmonary vascular remodeling, the improvement of right heart function, and the reduction of inflammatory response.

[0004] Ginsenoside F5 is a natural triterpene saponin, the molecular formula is C 41 H 70 O 13 , the molecular weight is 770.99, and the CAS number is 189513-26-6. The compound mainly exists in ginseng leaves and flower buds and belongs to trace saponin components. Researches show that the F group of ginsenosides has multiple biological activities, can inhibit inflammation and tumor growth, regulate immune homeostasis, reduce blood sugar and blood lipids, reduce vascular inflammation, inhibit vascular remodeling, protect myocardium and post-ischemic brain tissue, and improve energy metabolism disorder. However, no research shows that ginsenoside F5 is used for the prevention and treatment of PAH. SUMMARY

[0005] The technical problem to be solved by the present application is to provide an application of ginsenoside F5, which can effectively improve pulmonary vascular remodeling of pulmonary hypertension animals, reduce right ventricular systolic pressure, reduce right ventricular hypertrophy, and improve the survival rate of pulmonary hypertension animals, can inhibit pulmonary vascular remodeling and reduce pulmonary artery vascular injury. It is shown that ginsenoside F5 has a certain improvement effect on pulmonary hypertension, and is expected to become a new drug target for treating pulmonary hypertension, and can be used as a drug for preventing and treating pulmonary hypertension, and is used for preventing and improving pulmonary hypertension.

[0006] To solve the above technical problems, the technical scheme adopted by the present application is: an application of ginsenoside F5, the structural formula of the ginsenoside F5 is , the ginsenoside F5 is used for reducing right ventricular systolic pressure, reducing right ventricular hypertrophy index, reversing vascular remodeling of pulmonary hypertension, and reducing pulmonary artery vascular injury.

[0007] Preferably, the ginsenoside F5 is used for preparing a drug for preventing and / or improving pulmonary hypertension.

[0008] The present application has the following advantages compared with the prior art: The ginsenoside F5 of this invention can effectively improve pulmonary vascular remodeling in animals with pulmonary hypertension, reduce right ventricular systolic pressure, alleviate right ventricular hypertrophy, and improve the survival rate of animals with pulmonary hypertension. It can also inhibit pulmonary vascular remodeling and reduce pulmonary artery damage. This indicates that ginsenoside F5 has a certain ameliorative effect on pulmonary hypertension and is expected to become a new drug target for the treatment of pulmonary hypertension. It can be used as a class of drugs for the prevention and treatment of pulmonary hypertension.

[0009] The present invention will now be described in further detail with reference to the accompanying drawings and embodiments. Attached Figure Description

[0010] Figure 1 The figures show the survival rates of rats in the MCT-induced rat pulmonary hypertension animal model of Example 1 of this invention at different days in the control + solvent group, control + ginsenoside F5 group, MCT + solvent group, and MCT + ginsenoside F5 group. * in the figure indicates a significant difference of P < 0.05.

[0011] Figure 2 The following are right ventricular systolic pressure waveforms of the MCT-induced rat pulmonary hypertension animal model of Example 1 of this invention: control + solvent group, control + ginsenoside F5 group, MCT + solvent group, and MCT + ginsenoside F5 group. Figure 2 A) and right ventricular systolic pressure statistics ( Figure 2 B). *** in the figure indicates a significant difference (P < 0.001).

[0012] Figure 3 The figures show the right ventricular hypertrophy index of the MCT-induced rat pulmonary hypertension animal model in Example 1 of this invention: control + solvent group, control + ginsenoside F5 group, MCT + solvent group, and MCT + ginsenoside F5 group. ** in the figure indicates a significant difference of P < 0.005, and *** indicates a significant difference of P < 0.001.

[0013] Figure 4 These are representative images of hematoxylin-eosin (HE) staining of pulmonary vessels in the control + solvent group, control + ginsenoside F5 group, MCT + solvent group, and MCT + ginsenoside F5 group of the MCT-induced rat pulmonary hypertension animal model of Example 1 of the present invention. Detailed Implementation

[0014] Example 1 This embodiment describes the application of ginsenoside F5, the structural formula of which is: The ginsenoside F5 is used for reducing right ventricular systolic pressure, reducing right ventricular hypertrophy index, reversing vascular remodeling of pulmonary hypertension, and reducing pulmonary artery vascular injury, and is used for preparing a drug for preventing and / or improving pulmonary hypertension.

[0015] Specific experimental methods: (1) Establishment of a rat pulmonary hypertension animal model: Monocrotaline (MCT, from MCE Company, item number HY-N0750) is used to induce pulmonary hypertension in rats, which is a commonly used animal model of pulmonary hypertension. SD rats are subcutaneously injected with MCT 60 mg / kg once, and control rats are subcutaneously injected with the same volume of physiological saline ethanol solution (physiological saline ethanol solution: anhydrous ethanol and 0.9% sodium chloride injection are mixed at a volume ratio of 1:4) once. The modeling is completed after 21 days.

[0016] (2) Measurement of right ventricular systolic pressure (RVSP): After 3 weeks of MCT injection, the rats are anesthetized by inhaling 2% isoflurane, and the right ventricular systolic pressure is measured by inserting a PT-103N pressure sensor and a BL-420N signal acquisition and processing system (Chengdu Tailiang Software Co., Ltd.) into the right ventricle.

[0017] (3) Measurement of right ventricular hypertrophy index (RVHI): After blood pressure measurement, the rats are sacrificed, the heart is removed, the vascular roots and left and right atria are cut off, the right ventricular wall is carefully separated, and the right and left ventricles and interventricular septum are weighed after the water is absorbed with filter paper. The right ventricular hypertrophy index is calculated according to the formula: RVHI = RV / ( LV+S ). RV is the weight of the right ventricle; LV is the weight of the left ventricle; S is the weight of the interventricular septum.

[0018] (4) Pathological examination of lung tissue and pulmonary artery: The lower lobe of the right lung of the rat is taken, fixed with 4% paraformaldehyde for 24 hours, embedded in paraffin, and sliced continuously with a thickness of 5 μm. The lung tissue sections are used for HE staining.

[0019] The rat pulmonary hypertension animal model is used to explore the protective effect of ginsenoside F5 on pulmonary hypertension.

[0020] Experimental subjects: 8-10 weeks old healthy male SPF SD rats, weighing 200-250 g, purchased from Liaoning Changsheng Biotechnology Co., Ltd., and fed in the SPF animal room of Dalian Medical University. The feeding environment was maintained at room temperature of 20-25°C, relative humidity of 50-60%, illumination of 12h / d, and free water and food. The conventional rat feed was provided by Jiangsu Medison Biopharm Co., Ltd. The disposal of animals during the experiment conforms to the standard of animal ethics.

[0021] Experimental grouping: healthy SD rats were randomly divided into experimental and control groups according to the principle of weight balance. The experimental SD rats were subcutaneously injected with MCT (60 mg / kg) at one time, and then randomly divided into two groups according to the principle of weight balance, i.e. MCT+solvent group (the same volume of solvent as ginsenoside F5, intraperitoneal injection method) and MCT+ginsenoside F5 group (ginsenoside F5 10 mg / kg / day, intraperitoneal injection method). After 21 days, the modeling was completed, and the animal diet, water, activity, and death were observed. The control group of SD rats was subcutaneously injected with the same volume of physiological saline ethanol solution as MCT (physiological saline ethanol solution: mixed with anhydrous ethanol and 0.9% sodium chloride injection at a volume ratio of 1:4), and then randomly divided into two groups according to the principle of weight balance, i.e. control+solvent group (the same volume of solvent as ginsenoside F5, intraperitoneal injection method) and control+ginsenoside F5 group (ginsenoside F5 10 mg / kg / day, intraperitoneal injection method). After 21 days, the modeling was completed, and the animal diet, water, activity, and death were observed.

[0022] Experimental sampling: after the modeling was completed, the right ventricular systolic pressure of the SD rats was measured after anesthesia with 2% isoflurane inhalation, and then the weight of each ventricle and interventricular septum was measured, and the right ventricular hypertrophy index was calculated. Lung tissue was sectioned and pathologically stained to detect lung vascular pathological damage and evaluate the pulmonary vascular remodeling index.

[0023] Experimental results: 1. Ginsenoside F5 improves the survival rate of rats with pulmonary arterial hypertension.

[0024] MCT-induced pulmonary arterial hypertension rat model is one of the most widely used rodent PAH models, and its pathological features include pulmonary vascular remodeling, right ventricular hypertrophy, and progressive right heart failure, accompanied by significant mortality. The research results are as follows Figure 1The control group (control + solvent group and control + ginsenoside F5 group) animals did not occur death, while the experimental group (MCT + solvent group and MCT + ginsenoside F5 group) animals appeared death successively with the prolongation of PAH modeling time, and the mortality rate of MCT + solvent group reached 50% at about 40 days after modeling, while the mortality rate of MCT + ginsenoside F5 group was significantly lower than that of MCT + solvent group (20%, *P<0.05). It is suggested that ginsenoside F5 can significantly improve the survival rate of pulmonary arterial hypertension (PAH) model rats, and is expected to become a potential drug target for PAH treatment.

[0025] 2. Ginsenoside F5 can significantly reduce the right ventricular systolic pressure of pulmonary arterial hypertension rats.

[0026] The right ventricular systolic pressure of MCT-induced pulmonary arterial hypertension animal model can be significantly increased. The research results are shown in Figure 2 After modeling, the hemodynamic indexes of rats were measured using BL-420N signal acquisition system, and the right ventricular waveform is shown in Figure 2 A, the right ventricular systolic pressure of control group (control + solvent group and control + ginsenoside F5 group) rats is at normal level (<25 mmHg), while the right ventricular systolic pressure of experimental group (MCT + solvent group and MCT + ginsenoside F5 group) rats is significantly higher than that of control group (>25 mmHg). The right ventricular systolic pressure statistics are shown in Figure 2 B, the right ventricular systolic pressure of MCT + ginsenoside F5 group is significantly lower than that of MCT + solvent group. It is indicated that ginsenoside F5 can significantly reduce the right ventricular systolic pressure of pulmonary arterial hypertension rats, and has a remission effect on the clinical symptoms of PAH.

[0027] 3. Ginsenoside F5 can significantly inhibit the right ventricular hypertrophy of pulmonary arterial hypertension rats.

[0028] Pulmonary arterial hypertension rats will develop right ventricular hypertrophy due to persistent increase in pulmonary arterial pressure, and further cause right ventricular failure, and even death in severe cases. Right ventricular hypertrophy index is one of the core indicators for evaluating the progression of pulmonary arterial hypertension. The research results are shown in Figure 3 The right ventricular hypertrophy index of experimental group (MCT + solvent group and MCT + ginsenoside F5 group) rats is significantly increased compared with that of control group (control + solvent group and control + ginsenoside F5 group), while the right ventricular hypertrophy index of pulmonary arterial hypertension rats in MCT + ginsenoside F5 group is significantly lower than that in MCT + solvent group. It is indicated that ginsenoside F5 can significantly reduce the right ventricular hypertrophy index of pulmonary arterial hypertension rats, reduce the right ventricular function damage of pulmonary arterial hypertension animals, and has a protective effect on the right ventricular function.

[0029] 4. Ginsenoside F5 can significantly improve the pulmonary vascular remodeling of pulmonary arterial hypertension rats.

[0030] Pulmonary vascular remodeling is a typical pathological feature of pulmonary hypertension. The pulmonary vascular remodeling was evaluated by slicing the lung tissue and performing pathological HE staining. The results are shown in Figure 4 As shown in the results, compared with the control group (control + solvent group and control + ginsenoside F5 group), the experimental group (MCT + solvent group and MCT + ginsenoside F5 group) showed a significant increase in the thickness of the pulmonary vascular media and obvious vascular remodeling. However, compared with the MCT + solvent group, the MCT modeling + ginsenoside F5 group showed a significant decrease in the thickness of the vascular media and a significant reversal of vascular remodeling in pulmonary hypertension rats. This indicates that ginsenoside F5 can significantly inhibit pulmonary vascular remodeling in pulmonary hypertension rats and has a preventive and improving effect on pulmonary hypertension.

[0031] In summary, ginsenoside F5 can significantly improve the survival rate of MCT-induced pulmonary hypertension rats, reduce the right ventricular systolic pressure, inhibit right ventricular hypertrophy, effectively improve pulmonary vascular remodeling, and has a clear preventive and therapeutic effect on pulmonary hypertension. It is expected to become a potential target for the development of new drugs for this disease and can be used as a new type of drug for preventing and treating pulmonary hypertension. It can be used for the prevention and improvement of pulmonary hypertension. In addition, integrating traditional Chinese medicine into the prevention and treatment management system of major chronic diseases and promoting the innovative practice mode of integrated traditional Chinese and Western medicine has important significance for promoting academic progress and clinical translation in related fields.

[0032] The above is only a preferred embodiment of the present application, and does not limit the present application in any way. Any simple modification, change and equivalent change made according to the technical essence of the present application to the above embodiment are still within the protection scope of the technical solution of the present application.

Claims

1. An application of ginsenoside F5, characterized in that, The structural formula of ginsenoside F5 is as follows: The ginsenoside F5 is used to reduce right ventricular systolic pressure, reduce right ventricular hypertrophy index, reverse vascular remodeling of pulmonary hypertension, and reduce pulmonary artery vascular damage.

2. The application of ginsenoside F5 according to claim 1, wherein the ginsenoside F5 is used to prepare a drug for preventing and / or improving pulmonary hypertension.

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